rs6837818

chr4-184323-T-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642529.1(ZNF718):c.227-16758T>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,070 control chromosomes in the GnomAD database, including 4,480 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4480 hom., cov: 32)
• Consequence: ZNF718 ENST00000642529.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165

Genes affected

ZNF718 (HGNC:26889): (zinc finger protein 718) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription, DNA-templated. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF718	NR_110527.2	n.397-16758T>A		intron_variant, non_coding_transcript_variant
ZNF718	NR_110528.1	n.199-16758T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF718	ENST00000642529.1	c.227-16758T>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35454 AN: 151952 Hom.: 4480 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.0331

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.202

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.233 AC: 35447 AN: 152070 Hom.: 4480 Cov.: 32 AF XY: 0.231 AC XY: 17179 AN XY: 74364

Gnomad4 AFR AF: 0.176

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.0334

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.200

Alfa AF: 0.261 Hom.: 661

Bravo AF: 0.219

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	7.6
Dann	Benign	0.83

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6837818; hg19: chr4-178112;